Varicose ulcers are open skin sores that are caused by trauma to an area of the skin having poor blood flow. The vascular insufficiency renders the area extremely vulnerable to injury.
The trauma can be mechanical, such as a simple scratch or a laceration. This is the most common cause of varicose ulcers. Thermal trauma, from either heat or cold, can also lead to varicose ulcers. Chemicals can cause blistering, another form of trauma. Surgery is a fourth form of trauma. All of these forms of trauma to the skin can cause varicose ulcers.
The most common locations of varicose ulcers are the lower part of the legs and the feet (M. E. Levin in M. E. Levin et al., "The Diabetic Foot", 5th Edition, pages 17-59, Mosby-Year Book, Inc., 1993). Lower limbs which are affected with eczema or swelling are especially susceptible to varicose ulcers. Diabetics are more likely to have varicose ulcers than the general population.
Patients with varicose ulcers have symptoms such as burning, pain, leg discomfort while resting, walking pain, redness of the skin, and loss of hair, in addition to the open sores on the skin.
A neurotrophic ulcer is a disease of vascular origin occurring most often in patients affected with diabetes mellitus. The blood vessels of the lower extremities are affected most often, particularly the tibial and fibular arteries and their smaller branches. Patients suffering from neurotrophic ulcers have symptoms similar to patients suffering from varicose ulcers.
Several drugs, including pentoxifylline, have been used to treat varicose and neurotrophic ulcers (P. F. Adler, J. Foot Surgery, vol. 30, pages 300-303 (1991) and Ramani et al., Angiology, vol. 44, pages 623-626 (1993)). There are several disadvantages to the present drug treatments. Healing takes a long time, 90-120 days, a long period of time to suffer from open skin sores. In addition, many patients who start drug treatment of varicose and neurotrophic ulcers have to stop the treatment due to side effects or interactions with other medicines. Finally, the conventional drug treatments are not very effective in healing the ulcers.
The Adler study, referenced above, is a typical example of conventional drug treatment of skin ulcers. In this study, 12 diabetic patients affected with neurotrophic ulcers on their feet were treated with 400 mg of pentoxifylline, three times a day. Of the 12 patients, only 9 were able to complete the six month program because of side effects from the pentoxifylline. After 60 days, only 7 of the ulcers had healed. Another ulcer healed after 120 days. One was reduced in size from 4 cm to 2 cm after six months. This study illustrates that conventional drug treatment of patients suffering from varicose and neurotrophic ulcers has side effects and does not heal all of the ulcers.
Even after drug treatment, many patients must still undergo surgery to amputate the affected limb. Although overall statistics are not available, there are data on rates of amputation for diabetics. Diabetics are far more likely to suffer from neurotrophic ulcers than people who do not suffer from this disease. The global rate of amputation in diabetic patients is 15-40 times higher than for the general population. Furthermore, 50% of the patients who have a limb amputated are likely to have another amputation within the next five years. There is a clear need for a treatment for varicose and neurotrophic ulcers which can heal the ulcers in a shorter time and which has fewer side effects than traditional drug treatments.
Inner ear problems can cause body equilibrium problems such as dizziness and nausea. Such symptoms are very common. Body equilibrium disorders are the principal cause of consultation of general clinicians (W. Rubin, Modem Treatment, vol 6, page 54 (1976)). A recent study concluded that approximately 14 million people in the United States suffer from dizziness. There are other medical conditions related to the inner ear, such as poor hearing and tinnitus, or ringing in the ears.
Various drugs, including cinarizine, flunarizine, pentoxifylline, and Ginkgo biloba, have been used to treat dizziness, poor hearing, and tinnitus. All of these drugs have side effects. For example, all of the drugs cause nausea. Several have interactions with alcohol or other drugs. Several cause sleepiness. There is a need for a drug treatment for diseases of the inner ear, such as dizziness, poor hearing, and tinnitus that does not have side effects. There is a need for a rapid, effective treatment for the symptoms resulting from inner ear problems.
Hemorrhoids occur frequently in the general population. Hemorrhoids cause symptoms such as pain, burning, bleeding during defecation, and the appearance of protruding veins, particularly in the rectal area.
The normal treatment method for hemorrhoids is surgery to remove the protruding vein. The surgery can lead to difficulties such as pain and excessive bleeding. After the surgery, the patient must maintain a strict diet to minimize the chance of recurrence of the hemorrhoids. Even if the patient maintains the strict dietary regimen, the hemorrhoids can recur. There is a need for a nonsurgical treatment for hemorrhoids.
There is a need for a convenient and effective treatment for various diseases such as varicose and neurotrophic ulcers, diseases of the inner ear, and hemorrhoids. There is also a need for a treatment for these diseases that does not have the side effects of the present drug treatment methods.
Rosmarinus officinalis has previously been found to be a source of materials which have beneficial properties. For example, U.S. Pat. No. 4,318,906 to Llopart describes a liquid prepared from a blend of five plant oils, including an oil from Rosmarinus officinalis. The blend was found to be useful in treating wounds when applied to the surface of the skin. The blend was applied to an external varicose ulcer with a spray gun four to six times per day. The wound closed up after fourteen days and was completely healed after forty days. The need to spray the wound on such a frequent basis is inconvenient to the patient and could stain clothing. The healing time of forty days is a long period for the patient to suffer the symptoms of a varicose ulcer. There is a need for a more convenient and rapid method of treating varicose ulcers.
Rosmarinic acid has been isolated by extraction from Rosmarinus officinalis (Ricera Sci 1958, vol. 28, p 2392 to 2393 and Tetrahedron 1958, vol. 4, p 43 to 48). Extracts containing rosmarinic acid have been tested for stimulation of circulation (Deutsche Apotherker-Zeitung 1964, vol. 104 p. 287 to 289) and for antimicrobial activity (N. Z. Alimkhodzhaeva et al, Chemical Abstracts, vol. 82, 167491).
Wirtz-Peitz et al. (U.S. Pat. No. 4,358,442) prepared a rosmarinic acid-phospholipid complex which was found to have anti-inflammatory activity in rats. Isolating rosmarinic acid from plants is a complex process involving several steps, including extraction, drying, and recrystallization (U.S. Pat. No. 4,354,035). Reacting the purified rosmarinic acid with phospholipid and isolating the product further adds to the complexity and cost. There is a need for a product which can be made more conveniently and less expensively.
Extracts from rosemary leaves, stems or the like have also been used as food antioxidants. Chang et. al. isolated the active ingredient, Rosmaridiphenol, as disclosed in U.S. Pat. No. 4,638,095.
Accordingly, the objects of the present invention are to provide a method for isolating a dried total extract of Rosmarinus officinalis and to demonstrate its use in treating a variety of diseases, including: varicose and neurotrophic ulcers; diseases of the inner ear such as dizziness, poor hearing, and ringing in the ears; and hemorrhoids.